UCL Queen Square Institute of Neurology


Results of a ‘3 in 1’ trial for Progressive MS published

24 January 2020

Results of a clinical trial in progressive multiple sclerosis (MS) in which 3 different drugs were tested at the same time, instead of 1 by 1 by 1 have been published in The Lancet Neurology.

The MS-SMART trial is the largest such trial in progressive MS ever carried out.

Researchers said the novel trial design where tests for 3 drugs were completed in 5 years, instead of around 15 – the time it would have taken if trialled individually under usual practice – offers a template for future trials, which will speed up the process of drug discovery in neurological medicine.

Unfortunately – as announced when the study ended – the 3 drugs in the study were found not to be effective, despite positive early work in animals and humans.

Whilst being a simple concept, designing a trial with multiple drugs is a complex statistical exercise. But running a trial in this way is quicker than the traditional approach, and can be much less expensive.

The MS-SMART trial which took place in 13 centres around the UK, with UCL/H being the lead site, tested the safety and efficacy of 3 repurposed drugs (used for other conditions, but where experimental/early human work has shown some likely additional benefits in MS) in 445 people with secondary progressive MS – a later stage where the treatment opportunities are very limited.

Participants took amiloride (originally used to treat heart disease), riluzole (a treatment for motor neuron disease), fluoxetine (used for depression) or a placebo pill for two years. MRI scans and other clinical measures – such as walking, eyesight and thinking tests – were done before and after treatment to test for signs of slowing MS disease progression.

Professor Jeremy Chataway, Consultant Neurologist and lead researcher on the trial, based at UCL Queen Square Institute of Neurology, said: “Whilst of course we were disappointed with the results of the trial, we showed it was possible to successfully carry out a complex, ‘multi-arm’ trial in neurological disease, and Progressive MS in particular, which was much faster and cheaper to carry out than has traditionally been the case. Potential new treatments can be tested much more efficiently in future using this approach to trial design. We aim to do more trials like this, to get to effective treatment for Progressive MS quicker.”

MS is a neurological condition where the immune system attacks myelin, a substance surrounding the nerves, which affects the electrical signalling from the brain and spinal cord to the body. More women than man are affected and around 120,000 individuals in the UK are affected by it, with over 2 million worldwide.

It can affect movement, balance, vision and bladder function.

The trial was joint funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research partnership; the UK MS Society UK and the US National MS Society.



UCLH Biomedical Research Centre (BRC)